Early Intervention in Reducing Dietary Protein Intake Ameliorates Irreversible Mesangioproliferative Glomerulonephritis in Rats

We aimed to investigate the effects of early intervention in reducing dietary protein intake on chronic progressive GN (glomerulonephritis) by using an irreversible mesangioproliferative GN model. An irreversible mesangioproliferative GN model was induced by two injections of monoclonal anti Thy-1 antibody 1-22-3 two weeks apart. In Experiment 1, 10 rats were divided into a low protein diet (LPD: 6.4% protein) group and a normal protein diet (NPD: 25.4% protein) group. In Experiment 2, another 10 rats were divided into a high protein diet (HPD: 52.5% protein) group and an NPD group. After 10 weeks of administering an experimental diet, the rats were sacrificed to undergo blood biochemistry, light microscopy, and immunofluorescence analyses of the kidneys as well as a glomerular mRNA study. In the LPD group, urinary protein excretion and the expression of collagen type-I mRNA and protein all significantly decreased in comparison with the NPD group. In addition, the mesangial matrix expansion and the glomerular expression of α-smooth muscle actin (α-SMA) and transforming growth-factor-β (TGF-β) mRNA in the LPD group were lower than those in NPD group. However, in the HPD group, both TGF-β and collagen type-I glomerular mRNA expression were higher. The LPD therapy from the early stages of renal dysfunction can be considered effective in preventing further progression of the disease to chronic renal failure.